Genetic Variant MTM1:c.137-11delT (chrX-150598574-CT-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000252.3(MTM1):c.137-11delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000633 in 948,289 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000063 ( 0 hom. 0 hem. )

Consequence

MTM1
NM_000252.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.71

Publications

0 publications found

Variant links:

Genes affected

MTM1 (HGNC:7448): (myotubularin 1) This gene encodes a dual-specificity phosphatase that acts on both phosphotyrosine and phosphoserine. It is required for muscle cell differentiation and mutations in this gene have been identified as being responsible for X-linked myotubular myopathy. [provided by RefSeq, Jul 2008]

MTM1 Gene-Disease associations (from GenCC):

X-linked myotubular myopathy
Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P, Myriad Women’s Health, Ambry Genetics

MTM1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6

Variant X-150598574-CT-C is Benign according to our data. Variant chrX-150598574-CT-C is described in ClinVar as Benign. ClinVar VariationId is 2920027.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000252.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTM1	NM_000252.3	MANE Select	c.137-11delT	intron	N/A	NP_000243.1	Q13496-1
MTM1	NM_001376908.1		c.137-11delT	intron	N/A	NP_001363837.1	Q13496-1
MTM1	NM_001376906.1		c.137-11delT	intron	N/A	NP_001363835.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTM1	ENST00000370396.7	TSL:1 MANE Select	c.137-17delT	intron	N/A	ENSP00000359423.3	Q13496-1
MTM1	ENST00000689314.1		c.137-17delT	intron	N/A	ENSP00000510607.1	A0A8I5KZ76
MTM1	ENST00000866458.1		c.137-17delT	intron	N/A	ENSP00000536517.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000572

AC:

AN:

174696

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000129

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000633

AC:

AN:

948289

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

274561

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

23566

American (AMR)

AF:

0.00

AC:

AN:

34446

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18334

East Asian (EAS)

AF:

0.00

AC:

AN:

29354

South Asian (SAS)

AF:

0.00

AC:

AN:

50160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3374

European-Non Finnish (NFE)

AF:

0.00000706

AC:

AN:

707882

Other (OTH)

AF:

0.0000244

AC:

AN:

40963

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000195669), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.292

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Severe X-linked myotubular myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over